Pfeiffer Erika, Schebb Nils H, Podlech Joachim, Metzler Manfred
Institute of Applied Biosciences, Sections of Food Chemistry and Food Toxicology, University of Karlsruhe, D-76128 Karlsruhe, Germany.
Mol Nutr Food Res. 2007 Mar;51(3):307-16. doi: 10.1002/mnfr.200600237.
The Alternaria toxins alternariol (AOH; 3,7,9-trihydroxy-1-methyl-6H-benzo[c]chromen-6-one) and alternariol methyl ether (AME, 3,7-dihydroxy-9-methoxy-1-methyl-6H-benzo[c]chromen-6-one) are common contaminants of food and feed, but their oxidative metabolism in mammals is as yet unknown. We have therefore incubated AME and AOH with microsomes from rat, human, and porcine liver and analyzed the microsomal metabolites with HPLC and GC-MS/MS. Seven oxidative metabolites of AME and five of AOH were detected. Their chemical structures were derived from their mass spectra using deuterated trimethylsilyl (TMS) derivatives, and from the information obtained from enzymatic methylation. Several of the metabolites were identified by comparison with synthetic reference compounds. AME as well as AOH were monohydroxylated at each of the four possible aromatic carbon atoms and also at the methyl group. In addition, AME was demethylated to AOH and dihydroxylated to a small extent. As the four metabolites arising through aromatic hydroxylation of AME and AOH are either catechols or hydroquinones, the oxidative metabolism of these mycotoxins may be of toxicological significance.
链格孢毒素链格孢酚（AOH；3,7,9 - 三羟基 - 1 - 甲基 - 6H - 苯并[c]色烯 - 6 - 酮）和链格孢酚甲醚（AME，3,7 - 二羟基 - 9 - 甲氧基 - 1 - 甲基 - 6H - 苯并[c]色烯 - 6 - 酮）是食品和饲料中的常见污染物，但它们在哺乳动物体内的氧化代谢情况尚不清楚。因此，我们将AME和AOH与大鼠、人及猪肝微粒体一起孵育，并用高效液相色谱法（HPLC）和气相色谱 - 串联质谱法（GC - MS/MS）分析微粒体代谢产物。检测到了AME的7种氧化代谢产物和AOH的5种氧化代谢产物。它们的化学结构通过使用氘代三甲基硅烷基（TMS）衍生物的质谱以及酶促甲基化获得的信息推导得出。通过与合成参考化合物比较鉴定出了几种代谢产物。AME以及AOH在四个可能的芳香族碳原子中的每一个以及甲基上都发生了单羟基化。此外，AME发生了去甲基化生成AOH，并且有少量的双羟基化。由于AME和AOH通过芳香族羟基化产生的四种代谢产物要么是儿茶酚要么是对苯二酚，这些霉菌毒素的氧化代谢可能具有毒理学意义。
